We propose to examine multiple sclerosis brain tissue (both plaque and normal-appearing white matter), for the presence of macrophage subpopulations, based on the phenotypic expression of different monocyte/macrophage antigenic markers. We will use single and double immunoperoxidase staining methods with a panel of monoclonal and heterologous antibodies to identify the different macrophage populations, and their topographical relationship to lymphocytes (both T and B cells), and to endogenous brain cells in frozen multiple sclerosis brain tissues. Factors known to be produced by stimulated macrophages and lymphocytes (eg, interleukin-2, prostaglandins) will be investigated in multiple sclerosis brain tissue, using antibodies to these cell products. The origin of the central nervous system macrophages will be studied by testing for the antigens expressed on central nervous system macrophages, as compared with microglial cells. Results obtained from multiple sclerosis specimens will be compared to those from normal brain and from other neurological disease tissue. Much is known about the behavior and regulation of macrophages in lymphoid tissues. We will identify similarities and differences between macrophages in lymphoid tissue versus macrophages in multiple sclerosis brain tissue. This study will furnish information about the central nervous system macrophages, with implications as to the mechanism for controlling and modifying the function of these cells, thus providing data for new protocols in the treatment of multiple sclerosis.